This collaborative multiphase project is a continuous effort to investigate the immune response in both humans and experimental animals after their infection with human hepatitis C virus (HCV). In the initial phase, commercial testing kits were used to detect antibodies to HCV proteins in the known non-A and non-B hepatitis patient sera. This provided information on the serological data of HCV infection and its relationship to other clinical determinations. The second phase of the study will concentrate on identifying immune dominant epitopes and neutralizing epitopes. The scope of this phase of study will be extensive and timeconsuming. The third phase will encompass using knowledge of the immune response to develop a preventive strategy and understanding of the pathogenicity of this viral infection. Special attention will be paid to identifying the possible relationship between the immune response and the high chronicity in HCV-infected patients. One part of this study is to transfer the techniques and procedures developed in the laboratory studies to our clinical studies. We have developed a proliferation assay to measure the immune response in mice to recombinant HCV core proteins. We then adopted the experience learned in working with mice to develop procedures to differentiate chronic infected patients from recovered ones. During fiscal years 1995 and 1996, we initiated a new project to examine the potential for a nucleic acid vaccine for HCV. The knowledge, techniques, and material developed in this nucleic acid vaccine study will complement our continued effort to understand immune response in HCV infection. The long-term goals of both projects will lead to developing models of immune therapy for chronic viral infection of the liver.